Natural products provide a wide range of biologically active agents, many of which have unique profiles of pharmacological activity and therapeutic potential. Over four hundred alkaloids have been identified in extracts from amphibian skins. These include batrachotoxins, which are potent activators of sodium channels, histrionicotoxins, which are noncompetitive blockers of nicotinic receptor channel complexes and potassium channels, pumiliotoxins, which have myotonic and cardiotonic activity due to effects on sodium channels, and epibatidine, an extremely potent and selective nicotinic agonist with remarkable antinociceptive activity. Further alkaloids include 2,5-disubstituted decahydroquinolines, 3,5-disubstituted pyrrolizidines , 3,5-disubstituted indolizidines, 5,8-disubstituted indolizidines, 1,4-disubstituted and 4,6-disubstituted quinolizidines, the pumiliotoxin-homopumiliotoxin-allopumiliotoxin class, and a variety of tricyclic alkaloids, including pyrrolizidine oximes, pseudophrynamines, cyclopentaquinolizidines and coccinellines. Most of these alkaloids have been detected and characterized from neotropical dendrobatid frogs. Pumiliotoxins also occur in one genus of Australian myobatrachid frogs, in one genus of South American bufonid toads and in one genus of Madagascan mantellid frogs. It appears all frog skin alkaloids have a dietary origin, being taken up and sequestered unchanged into skin glands. Ants, beetles and millipedes appear to be the source of certain frog skin alkaloids. Decahydroquinolines have now been discovered in ants. The origin of the batrachotoxins, histrionicotoxins, pumiliotoxins, and epibatidines found in frog skin remains a mystery. Structures have now been determined for a 1,4-disubstituted quinolizidine, a trisubstituted indolizidine, a novel tricyclic alkaloid related to the coccinellines, a dimeric decahydroquinoline, a set of nineteen-carbon decahydroquinolines from frogs and ants and an oxirane-containing allopumiliotoxin. Spiropyrrolizidine oximes, pseudophrynaminol, a series of tropane alkaloids (potential muscarinic/nicotinic agonists) and a methylisooxazole analog (epiboxidine) of the potent nicotinic analgetic epibatidine have been synthesized for biological evaluation.